Attitude towards and experience with SARS-CoV-2 vaccination among German cancer patients

Background: Cancer patients (pts) were among the first to receive vaccination against SARS-CoV-2 (vac). However, their attitude towards as well as experience with vac remain unclear. Methods: Between 04-11/2021 cancer pts at our university cancer center completed a baseline (BL) and follow-up (FU) questionnaire (Q) containing multiple choice questions and ten eleven-level Likert items ranging from 1 (“totally disagree”) to 11 (“totally agree”). Data was analyzed using Student's t-test or Chi-square test. Results: 219 pts (43% female) completed BLQ (110 FUQ). Mean age was 64 (24-87) years. 82% had solid tumors, 93% were on active therapy (80% chemotherapy). 4% had history of COVID-19. 78% had already received at least one vac at BL, mainly BNT162b2 (91%) or ChAdOx1-S (8%). Only 1% refused vac. Most pts completely agreed to “definitely get vaccinated” (82%) and completely disagreed with “vac is dispensable due to COVID-19 being no serious threat” (82%;more dissent among men, p = 0.037) or “being against vaccination in general” (81%). Self-assessment as member of a risk group (p = 0.03) and fear of COVID-19 (p = 0.002) were more common among women. Every third patient (31%) completely agreed to “being afraid of COVID-19”, every second thinks “SARSCoV-2 infection would be very dangerous” (56%). Only 41% expressed “complete confidence in the vaccine being safe” and 37% “not being afraid of side effects”. Fear of side effects (SE) was more common among women (p = 0.0016), pts with solid tumors (p = 0.05), with GI tumors (p < 0.0001) and below mean age (p = 0.006). The latter expressed less “confidence in the vaccine being safe” (p = 0.0029). At FUQ, most pts (91%) reported their vac to be well tolerated, 44% reported no SE, especially men (p = 0.001) and pts above age average (p = 0.002). Most common SE was local pain at injection site (36%), which was more frequent among women (p = 0.002), younger pts (p = 0.024) and pts with solid tumors (p = 0.04). Other common SE included fatigue (18%) and myalgia (8%). No thromboembolic events occurred. Only 3 pts had their therapy postponed due to SE. Almost all pts felt retrospectively sufficiently informed about vac and possible SE (94%), would have it again (88%) and agree to get it yearly, if recommended (78%). After vac, pts felt safe meeting friends or family (91%) or shopping (62%). Vacation (32%), work (22%), public transport (21%) or sports (19%) were considered less safe (less frequent among men, p < 0.05). Most pts (70%) did not feel that the COVID-19 pandemic negatively influenced their treatment and regarded the hospitals protective measures as adequate (91%). Conclusions: Willingness to get vac is high among cancer pts and vac is well tolerated in this sensitive cohort. However, concerns about vac safety remain an issue. Those as well as gender differences need to be addressed to increase vac rates and tolerability. The present results may help identify pts that benefit from more detailed pre-vac consultation.

DIFFERENT HUMORAL but SIMILAR CELLULAR RESPONSES of PATIENTS with AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES under DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS after COVID-19 VACCINATION

Background: The interplay between humoral and cellular response after vaccination against SARS-CoV-2 in patients (pts.) with autoimmune infammatory rheumatic diseases (AIRD) remains unknown. Objectives: To investigate the impact of different immunosuppressive therapies on the development of humoral and cellular immune responses to full 2-dose SARS-CoV-2 vaccination in AIRD pts. with stable low disease activity. Methods: The immune reactivity to COVID-19 vaccination was investigated in a prospectively recruited AIRD cohort with rheumatoid arthritis, axial spondy-loarthritis or psoriatic arthritis which received a therapy with IL-17i, TNFi, JAKi or MTX (alone or in combination). Almost all patients received mRNA-based vaccine, only 4 patients had a heterologous scheme. Anti-spike(S) antibodies(ab.) and sera neutralizing capacity (neutralization dilution 50;ND50) were measured 4 weeks after the frst (prime+4w) and 4 weeks after the second vaccination (boost+4w). Vaccine-specifc cellular immunity was evaluated by quantifying expression of activation markers on T cells as well as their production of key cytokines, at prime+4w and boost+4w. Results: Overall, a total of 92 pts. were included in the fnal cohort. 31 (33.7%) pts. were on TNFi, 24 (26.1%) on IL-17i, 24 (26.1%) on JAKi, each group encompassing pts. receiving drug inhibitors alone or in combination with MTX.13 (14.1%) were treated with MTX alone. The median time between the vaccination and blood sampling was 31 [IQR: 28-34] days after prime+4w and 28 [IRQ: 28-28] days after boost+4w. Although at prime+4w only 34/90 (37.8%) of pts. presented neutralizing ab., the majority (86/91, 94.5%), developed them at boost+4w. The highest neutralization titer developed the pts. on IL-17i both at prime+4w (74 [IQR: 13-91]) and boost+4w (798 [IQR: 511-1344]), while no statistically signifcant differences were found in the neutralization titer at boost+4w for the TNFi, JAKi, and MTX groups: 207 ND50 [IQR: 120-576], 319 [IQR: 133-461] and 749 [IQR: 264-1920], respectively. 81/90 (90.0%) pts. developed IgG ab. against SARS-CoV-2 S-protein at prime+4w and 91/92 (98.9%) at boost+4w. Pts. receiving IL-17i developed higher ab. titers (8295 U/mL [IQR: 4586-11,237]) compared to the other three groups: JAKi (4405 U/mL [IQR: 1436-7265], TNFi (2313 [IQR: 1156-3630] U/mL) and MTX (2010 U/mL [IQR: 693-9254]). Neutralization capacity correlated well with the titer of anti-S ab. at both timepoints. Co-administration of biologic/tsDMARDs and MTX led to lower titers compared to biologic/tsDMARDs mon-otherapy. All therapies left frequencies of CD154+CD137+ CD4+ T cells and CD137+ CD8+ T cells at prime+4w and boost+4w unchanged. Polyfunction-ality and T cell cytokine profiles across therapies did not signifcantly vary at boost+4w. Conclusion: Even after insufficient seroconversion for neutralizing capacity and ab. response against SARS-CoV-2 S-proteins between pts. of different mod of action agents, particularly for MTX and JAKi after frst vaccination, a second vaccination covered almost all pts. regardless of DMARDs therapy, with better outcomes in those on IL-17I. T cell immunity revealed similar frequencies of activated T cells in all modes of action after the second vaccination.

Preserved T-cellresponse in B-cell depleted patientsfollowing SARS-CoV-2 vaccination

Objective: To investigate the humoral and T-cell immune response of multiple sclerosis (MS) patients under B-cell depleting therapy following SARS-CoV-2 vaccination compared to healthy controls (HC). Background: The SARS-CoV-2 pandemic has huge implications for the management of patients with MS under highly active immune therapies. First reports indicated that the humoral response of anti-CD20 treated, B-cell depleted patients might by attenuated. Data about dynamics of B-cell repopulation and T-cell response are scarce. Design/Methods: The study was authorized by the local ethics committee of the RuhrUniversity Bochum. Patients were recruited at the Department of Neurology. We included n=10 healthy age-matched controls and n=37 B-cell depleted MS patients (20 ocrelizumab, 17 off-label rituximab). Serum and Peripheral Blood Mononuclear Cells (PBMCs) were isolated 4-8 weeks after second vaccination. Serum was analyzed for anti-SARS-CoV-2-Spike antibodies. Lymphocyte subpopulations were analyzed in B-cell depleted patients by FACS analysis. PBMCs were stimulated with 2 μg/ml SARS-CoV-2 peptide-mix for 16-18 hours and analyzed via flow cytometry for cytokine-expressing T-cell populations. Results: 15/36 (40.5%) patients mounted an antibody response >10 U/ml (range 0.8-2,500). The anti-SARS-CoV-2-Spike titer correlated with B-cell repopulation (R2 =0.01841;r=0.4481;p=0.0069), whereas no significance could be detected correlating with the time to last infusion (R2 =0.1352;r=0.3058;p=0.0740). On the contrary, T-cell responses of B-cell depleted patients were higher or did not deviate from those of HC. Frequencies of CD4+ -T-cells expressing IFN-γ or IL-4 and CD8+ -T-cells expressing IFN-γ or IFN-γ and IL-2 were significantly higher in B-cell depleted patients, while CD4+ -T-cells expressing IL-2 or IFN-γ and IL-2 as well as CD8+ -T-cells expressing IL-2 did not differ from HC. Conclusions: Humoral vaccination responses in B-cell depleted patients are dependent on B-cell repopulation. Notably, patients with poor humoral response are able to mount a sustained T-cell response after SARS-CoV-2 vaccination. Those data suggest, that vaccinated B-cell depleted patients might be partially protected against SARS-CoV-2 infection.

Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2.

The highest viral loads of severe acute respiratory syndrome coronavirus-2 are detectable in the oral cavity, so a potential reduction of infectious virus by nasal and oral sprays could reduce transmission. Therefore, the inactivation capacity of nine nasal and oral sprays was evaluated according to EN 14476. One nasal spray based on sodium hypochlorite and one oral spray containing essential oils reduced viral titres by two to three orders of magnitude. Although clinical data are still sparse, nasal and oral sprays display a more convenient application for elderly people or those who are unable to rinse/gargle.

Virucidal potential of oral rinses and nasal sprays against SARS-COV-2 and their mode of action

Introduction: The ongoing SARS-CoV-2 pandemic creates a significant threat to global health. Recent studies suggested the significance of throat and salivary glands as major sites of virus replication and transmission during early COVID-19 thus advocating application of oral antiseptics. Objectives: Here, we evaluated the virucidal activity of different available oral rinses, nasal sprays as well as individual compounds found in oral rinses against SARS-CoV-2. These experiments were performed under conditions mimicking nasopharyngeal secretions and investigated their respective virucidal modes of action. Methods: According to European guidelines, virucidal activity was determined with a quantitative suspension test with 30 s exposure time on VeroE6 cells. Mechanistic analysis to reveal the mode of action of antiseptic agents included density gradient centrifugation and a capsid protection assay. Results: Three of the eight oral rinses as well as two nasal sprays significantly reduced viral infectivity to up to three orders of magnitude to background levels. Mechanistic analysis revealed that treatment with benzalconiumchloride and other antiseptic agents used in mouth rinses primarily disrupted the viral envelope, without affecting viral RNA integrity. Conclusion: In summary, we provide evidence that SARS-CoV-2 can be efficiently inactivated by commercially available oral rinses and nasal sprays with respect to their compound composition, within short exposure times, thus possibly lowering the transmission of SARS-CoV-2.

Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2.

During the current SARS-CoV-2 pandemic new studies are emerging daily providing novel information about sources, transmission risks and possible prevention measures. In this review, we aimed to comprehensively summarize the current evidence on possible sources for SARS-CoV-2, including evaluation of transmission risks and effectiveness of applied prevention measures. Next to symptomatic patients, asymptomatic or pre-symptomatic carriers are a possible source with respiratory secretions as the most likely cause for viral transmission. Air and inanimate surfaces may be sources; however, viral RNA has been inconsistently detected. Similarly, even though SARS-CoV-2 RNA has been detected on or in personal protective equipment (PPE), blood, urine, eyes, the gastrointestinal tract and pets, these sources are currently thought to play a negligible role for transmission. Finally, various prevention measures such as handwashing, hand disinfection, face masks, gloves, surface disinfection or physical distancing for the healthcare setting and in public are analysed for their expected protective effect.

Virucidal efficacy of different formulations for hand and surface disinfection targeting SARS CoV-2.

In the ongoing SARS CoV-2 pandemic, effective disinfection measures are needed, and guidance based on the methodological framework of the European Committee for Standardization (CEN) may enable the choice of effective disinfectants on an immediate basis. This study aimed to elucidate whether disinfectants claiming 'virucidal activity against enveloped viruses' as specified in the European Standard EN 14476 as well as in the German Association for the Control of Viral Diseases/Robert Koch Institute (DVV/RKI) guideline are effectively inactivating SARS-CoV-2. Two commercially available formulations for surface disinfection and one formulation for hand disinfection were studied regarding their virucidal activity. Based on the data of this study the enveloped SARS-CoV-2 is at least equally susceptible compared to the standard test virus vaccinia used in the EN 14476 and DVV/RKI guidelines. Thus, chemical disinfectants claiming 'virucidal activity against enveloped viruses' based on the EN 14476 and DVV/RKI guidelines will be an effective choice to target enveloped SARS-CoV-2 as a preventive measure.

In Vitro Lung Models and Their Application to Study SARS-CoV-2 Pathogenesis and Disease

SARS-CoV-2 has spread across the globe with an astonishing velocity and lethality that has put scientist and pharmaceutical companies worldwide on the spot to develop novel treatment options and reliable vaccination for billions of people. To combat its associated disease COVID-19 and potentially newly emerging coronaviruses, numerous pre-clinical cell culture techniques have progressively been used, which allow the study of SARS-CoV-2 pathogenesis, basic replication mechanisms, and drug efficiency in the most authentic context. Hence, this review was designed to summarize and discuss currently used in vitro and ex vivo cell culture systems and will illustrate how these systems will help us to face the challenges imposed by the current SARS-CoV-2 pandemic.

Comparison of the in-vitro efficacy of different mouthwash solutions targeting SARS-CoV-2 based on the European Standard EN 14476

The outbreak of the SARS-CoV-2 pandemic is triggering a global health emergency alert. Until vaccination becomes available, a bundle of effective preventive measures is desperately needed. Recent research is indicating the relevance of aerosols in the spread of SARS-CoV-2. Thus, in this study commercially available antiseptic mouthwashes based on the active ingredients chlorhexidine digluconate and octenidine dihydrochloride (OCT) were investigated regarding their efficacy against SARS-CoV-2 using the European Standard 14476. Based on the requirement of EN 14476 in which reduction of at least four decimal logarithms (>=4 log₁₀) of viral titre is requested to state efficacy, the OCT-based formulation was found to be effective within a contact time of only 15 s against SARS-CoV-2. Based on this in-vitro data the OCT mouthwash thus constitutes an interesting candidate for future clinical studies to prove its effectiveness in a potential prevention of SARS-CoV-2 transmission by aerosols.

Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.

Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.